Intravenous Busulfan Compared with Total Body Irradiation Pretransplant Conditioning for Adults with Acute Lymphoblastic Leukemia

Acute Leukemia Committee of the CIBMTR, Partow Kebriaei, Claudio Anasetti, Mei Jie Zhang, Hai Lin Wang, Ibrahim Aldoss, Marcos de Lima, H. Jean Khoury, Brenda M. Sandmaier, Mary M. Horowitz, Andrew Artz, Nelli Bejanyan, Stefan Ciurea, Hillard M. Lazarus, Robert Peter Gale, Mark Litzow, Christopher Bredeson, Matthew D. Seftel, Michael A. Pulsipher, Jaap Jan Boelens & 31 others Joseph Alvarnas, Richard Champlin, Stephen Forman, Vinod Pullarkat, Daniel Weisdorf, David I. Marks, William Hogan, Minoo Battiwalla, Edward Copelan, Gerhard Hildebrandt, Sid Ganguly, Navneet Majhail, Ann Woolfrey, Ian Nivison-Smith, Mark Hertzberg, Miguel Angel Diaz, Ann Jakubowski, Celalettin Ustun, Agnes Yong, Cesar Freytes, Zachariah DeFilipp, Yoshi Inamoto, Jean Yves Cahn, Bipin Savani, Jean Yared, Ashish Bajel, Ulrike Bacher, Geoffrey Uy, David Rizzieri, Matthew Wieduwilt, Kirk Schultz

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Total body irradiation (TBI) has been included in standard conditioning for acute lymphoblastic leukemia (ALL) before hematopoietic cell transplantation (HCT). Non-TBI regimens have incorporated busulfan (Bu) to decrease toxicity. This retrospective study analyzed TBI and Bu on outcomes of ALL patients 18–60 years old, in first or second complete remission (CR), undergoing HLA-compatible sibling, related, or unrelated donor HCT, who reported to the Center for International Blood and Marrow Transplant Research from 2005 to 2014. TBI plus etoposide (25%) or cyclophosphamide (75%) was used in 819 patients, and intravenous Bu plus fludarabine (41%), clofarabine (30%), cyclophosphamide (15%), or melphalan (13%) was used in 299 patients. Bu-containing regimens were analyzed together, since no significant differences for patient outcomes were noted between them. Bu patients were older, with better performance status; took longer to achieve first CR and receive HCT; were treated more recently; and were more likely to receive peripheral blood grafts, antithymocyte globulin, or tyrosine kinase inhibitors. With median follow-up of 3.6 years for Bu and 5.3 years for TBI, adjusted 3-year outcomes showed treatment-related mortality Bu 19% versus TBI 25% (P =.04); relapse Bu 37% versus TBI 28% (P =.007); disease-free survival (DFS) Bu 45% versus TBI 48% (P =.35); and overall survival (OS) Bu 57% versus TBI 53% (P =.35). In multivariate analysis, Bu patients had higher risk of relapse (relative risk, 1.46; 95% confidence interval, 1.15 to 1.85; P =.002) compared with TBI patients. Despite the higher relapse, Bu-containing conditioning led to similar OS and DFS following HCT for ALL.

LanguageEnglish
Pages726-733
Number of pages8
JournalBiology of Blood and Marrow Transplantation
Volume24
Issue number4
DOIs
Publication statusPublished - 1 Apr 2018

Keywords

  • Acute lymphoblastic leukemia
  • Allogeneic transplant
  • Busulfan
  • Total body irradiation

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

@article{2c0943600eae4d4f831257b05d67c398,
title = "Intravenous Busulfan Compared with Total Body Irradiation Pretransplant Conditioning for Adults with Acute Lymphoblastic Leukemia",
abstract = "Total body irradiation (TBI) has been included in standard conditioning for acute lymphoblastic leukemia (ALL) before hematopoietic cell transplantation (HCT). Non-TBI regimens have incorporated busulfan (Bu) to decrease toxicity. This retrospective study analyzed TBI and Bu on outcomes of ALL patients 18–60 years old, in first or second complete remission (CR), undergoing HLA-compatible sibling, related, or unrelated donor HCT, who reported to the Center for International Blood and Marrow Transplant Research from 2005 to 2014. TBI plus etoposide (25{\%}) or cyclophosphamide (75{\%}) was used in 819 patients, and intravenous Bu plus fludarabine (41{\%}), clofarabine (30{\%}), cyclophosphamide (15{\%}), or melphalan (13{\%}) was used in 299 patients. Bu-containing regimens were analyzed together, since no significant differences for patient outcomes were noted between them. Bu patients were older, with better performance status; took longer to achieve first CR and receive HCT; were treated more recently; and were more likely to receive peripheral blood grafts, antithymocyte globulin, or tyrosine kinase inhibitors. With median follow-up of 3.6 years for Bu and 5.3 years for TBI, adjusted 3-year outcomes showed treatment-related mortality Bu 19{\%} versus TBI 25{\%} (P =.04); relapse Bu 37{\%} versus TBI 28{\%} (P =.007); disease-free survival (DFS) Bu 45{\%} versus TBI 48{\%} (P =.35); and overall survival (OS) Bu 57{\%} versus TBI 53{\%} (P =.35). In multivariate analysis, Bu patients had higher risk of relapse (relative risk, 1.46; 95{\%} confidence interval, 1.15 to 1.85; P =.002) compared with TBI patients. Despite the higher relapse, Bu-containing conditioning led to similar OS and DFS following HCT for ALL.",
keywords = "Acute lymphoblastic leukemia, Allogeneic transplant, Busulfan, Total body irradiation",
author = "{Acute Leukemia Committee of the CIBMTR} and Partow Kebriaei and Claudio Anasetti and Zhang, {Mei Jie} and Wang, {Hai Lin} and Ibrahim Aldoss and {de Lima}, Marcos and Khoury, {H. Jean} and Sandmaier, {Brenda M.} and Horowitz, {Mary M.} and Andrew Artz and Nelli Bejanyan and Stefan Ciurea and Lazarus, {Hillard M.} and Gale, {Robert Peter} and Mark Litzow and Christopher Bredeson and Seftel, {Matthew D.} and Pulsipher, {Michael A.} and Boelens, {Jaap Jan} and Joseph Alvarnas and Richard Champlin and Stephen Forman and Vinod Pullarkat and Daniel Weisdorf and Marks, {David I.} and William Hogan and Minoo Battiwalla and Edward Copelan and Gerhard Hildebrandt and Sid Ganguly and Navneet Majhail and Ann Woolfrey and Ian Nivison-Smith and Mark Hertzberg and Diaz, {Miguel Angel} and Ann Jakubowski and Celalettin Ustun and Agnes Yong and Cesar Freytes and Zachariah DeFilipp and Yoshi Inamoto and Cahn, {Jean Yves} and Bipin Savani and Jean Yared and Ashish Bajel and Ulrike Bacher and Geoffrey Uy and David Rizzieri and Matthew Wieduwilt and Kirk Schultz",
year = "2018",
month = "4",
day = "1",
doi = "10.1016/j.bbmt.2017.11.025",
language = "English",
volume = "24",
pages = "726--733",
journal = "Biology of Blood and Marrow Transplantation",
issn = "1083-8791",
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Intravenous Busulfan Compared with Total Body Irradiation Pretransplant Conditioning for Adults with Acute Lymphoblastic Leukemia. / Acute Leukemia Committee of the CIBMTR.

In: Biology of Blood and Marrow Transplantation, Vol. 24, No. 4, 01.04.2018, p. 726-733.

Research output: Contribution to journalArticle

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T1 - Intravenous Busulfan Compared with Total Body Irradiation Pretransplant Conditioning for Adults with Acute Lymphoblastic Leukemia

AU - Acute Leukemia Committee of the CIBMTR

AU - Kebriaei, Partow

AU - Anasetti, Claudio

AU - Zhang, Mei Jie

AU - Wang, Hai Lin

AU - Aldoss, Ibrahim

AU - de Lima, Marcos

AU - Khoury, H. Jean

AU - Sandmaier, Brenda M.

AU - Horowitz, Mary M.

AU - Artz, Andrew

AU - Bejanyan, Nelli

AU - Ciurea, Stefan

AU - Lazarus, Hillard M.

AU - Gale, Robert Peter

AU - Litzow, Mark

AU - Bredeson, Christopher

AU - Seftel, Matthew D.

AU - Pulsipher, Michael A.

AU - Boelens, Jaap Jan

AU - Alvarnas, Joseph

AU - Champlin, Richard

AU - Forman, Stephen

AU - Pullarkat, Vinod

AU - Weisdorf, Daniel

AU - Marks, David I.

AU - Hogan, William

AU - Battiwalla, Minoo

AU - Copelan, Edward

AU - Hildebrandt, Gerhard

AU - Ganguly, Sid

AU - Majhail, Navneet

AU - Woolfrey, Ann

AU - Nivison-Smith, Ian

AU - Hertzberg, Mark

AU - Diaz, Miguel Angel

AU - Jakubowski, Ann

AU - Ustun, Celalettin

AU - Yong, Agnes

AU - Freytes, Cesar

AU - DeFilipp, Zachariah

AU - Inamoto, Yoshi

AU - Cahn, Jean Yves

AU - Savani, Bipin

AU - Yared, Jean

AU - Bajel, Ashish

AU - Bacher, Ulrike

AU - Uy, Geoffrey

AU - Rizzieri, David

AU - Wieduwilt, Matthew

AU - Schultz, Kirk

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Total body irradiation (TBI) has been included in standard conditioning for acute lymphoblastic leukemia (ALL) before hematopoietic cell transplantation (HCT). Non-TBI regimens have incorporated busulfan (Bu) to decrease toxicity. This retrospective study analyzed TBI and Bu on outcomes of ALL patients 18–60 years old, in first or second complete remission (CR), undergoing HLA-compatible sibling, related, or unrelated donor HCT, who reported to the Center for International Blood and Marrow Transplant Research from 2005 to 2014. TBI plus etoposide (25%) or cyclophosphamide (75%) was used in 819 patients, and intravenous Bu plus fludarabine (41%), clofarabine (30%), cyclophosphamide (15%), or melphalan (13%) was used in 299 patients. Bu-containing regimens were analyzed together, since no significant differences for patient outcomes were noted between them. Bu patients were older, with better performance status; took longer to achieve first CR and receive HCT; were treated more recently; and were more likely to receive peripheral blood grafts, antithymocyte globulin, or tyrosine kinase inhibitors. With median follow-up of 3.6 years for Bu and 5.3 years for TBI, adjusted 3-year outcomes showed treatment-related mortality Bu 19% versus TBI 25% (P =.04); relapse Bu 37% versus TBI 28% (P =.007); disease-free survival (DFS) Bu 45% versus TBI 48% (P =.35); and overall survival (OS) Bu 57% versus TBI 53% (P =.35). In multivariate analysis, Bu patients had higher risk of relapse (relative risk, 1.46; 95% confidence interval, 1.15 to 1.85; P =.002) compared with TBI patients. Despite the higher relapse, Bu-containing conditioning led to similar OS and DFS following HCT for ALL.

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KW - Allogeneic transplant

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